Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia.
Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia.
Sci Adv. 2023 May 10;9(19):eadf2384. doi: 10.1126/sciadv.adf2384.
The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine ( = 23) and human ( = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse ( = 8) and human ( = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% ( = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.
皮肤角质细胞癌（KC）的主要致癌因素是紫外线（UV）辐射。越来越多的证据表明，突变积累和克隆扩增在 KC 发展中起着关键作用。UV 暴露、表皮突变负荷和 KC 之间的关系尚不清楚。在这里，我们检查了小鼠（= 23）和人类（= 37）表皮样本中的突变负荷。表皮突变呈剂量依赖性积累，且突变负荷与 KC 负担相关。在小鼠（= 8）和人类（= 6）临床试验中，表皮消融（机械或激光诱导），随后自发愈合，可明显降低表皮突变负荷。在 UV 诱导的基底细胞癌模型中，表皮消融可使新发病变减少 80%以上（= 5）。总的来说，我们的研究结果表明，突变负荷与 KC 负担密切相关，是预防后续 KC 的靶点。
